PROJECT 2: ANATOMICAL BASIS OF DECISION-MAKING The overall aim of this project is the continued investigation of the neurobiogical basis of decision-making, guided by a systems-level neuroanatomical and cognitive framework for decision-making. This framework posits that decision-making defects in the personal and social realms are the result of a defective engagement of emotion-related signals that normally operate, covertly or overtly, to facilitate the process of making advantageous choices. In the current funding period, we provided new evidence in support of the notion that: (1) the neural systems subserving decision-making and social functioning overlap with those subserving emotions and feelings;(2) the vagus nerves are possible conduits for the emotion-related, signals that play a critical role in decision-making;(3) the right ventromedial prefrontal cortex may be more critical than the left for social conduct, decision-making, and emotional processing;and that (4) emotions may have a disruptive role in certain kinds of decisions. Guided by these results, the new studies we propose aim at (1) exploring the neural substrates supporting different types of decisions, and investigating the role of emotions in each type;(2) addressing the possible gender-related differences in decision-making; and (3) addressing new challenges to the interpretation of our past experiments on decision-making. The studies call for the testing of several hypotheses using the lesion approach in cognitive and psychophysiological experiments. Public health relevance: Disorders of decision-making are a prominent feature of the "dysexecutive syndrome" seen in stroke, head injury, and brain tumors. Such disorders are also prevalent in drug addiction, psychopathy, and borderline personality disorder. Our results will contribute to the understanding of pathological mechanisms of decision-making and lead to the development of novel therapeutic and management strategies for these disorders. In addition to these benefits to public health, our results are likely to contribute to the emerging field of neuroeconomics, a promising hybrid combining the neural investigation of decision-making with behavioral economics. Few areas of the life sciences are as exciting, and even fewer offer the same potential for understanding human nature while also making an impact in medicine.